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Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events III (TRACE III): a randomised, phase III, open- label, controlled trial

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Stroke & vascular neurology 2024年第1期9卷 82-89页

作者： Yunyun Xiong Bruce C V Campbell Marc Fisher Lee H Schwamm Mark Parsons Hao Li Yuesong Pan Xia Meng Xingquan Zhao Yongjun Wang neurology Beijing Tiantan HospitalBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina Department of Medicine and neurology The University of MelbourneMelbourneVictoriaAustralia neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA Department of neurology and Comprehensive Stroke Center Massachusetts General HospitalBostonMassachusettsUSA Department of neurology University of New South Wales South Western Sydney Clinical SchoolLiverpoolNew South WalesAustralia

Background and purpose Recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)was not inferior to alteplase for ischaemic stroke within *** study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion(LVO)of anterior circulation beyond *** and design Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III(TRACE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical *** who had an ischaemic stroke due to anterior circulation LVO(internal carotid artery,middle cerebral artery M1 and M2 segments)within 4.5–24hours from last known well(including wake-up stroke and no witness stroke)and with salvageable tissue(ischaemic core volume6s at 24 hours and NIHSS score change from baseline at *** outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 *** TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond *** registration number NCT05141305.

关键词： Therapy random Rational

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Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

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Neural Regeneration Research 2024年第10期19卷 2229-2239页

作者： Yubo Wang Ling Zhang Tianjie Lyu Lu Cui Shunying Zhao Xuechun Wang Meng Wang Yongjun Wang Zixiao Li vascular neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke

关键词： DNA demethylation DNA methylation DNMT3A functional outcome hyperinflammatory state interleukin neuroinflammation stroke TET2

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GM-CSF Promotes the Development of Dysfunctional vascular Networks in Moyamoya Disease

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Neuroscience Bulletin 2024年第4期40卷 451-465页

作者： Huiqin Li Xiang Cao Xinya Gu Mengqi Dong Lili Huang Chenglu Mao Shengnan Xia Haiyan Yang Xinyu Bao Yongbo Yang Yun Xu Department of neurology and Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of neurology and Neurosurgery Nanjing Drum Tower HospitalState Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical DiseasesNanjing UniversityNanjing210008China Department of neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjing210008China Department of neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of neurology Nanjing210008China Nanjing neurology Medical Center Nanjing210008China

Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal *** inflammation is associated with the occurrence and development of ***,the mechanisms underlying the formation of the abnormal vascular network remain ***-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(Pvascular networks in MMD.

关键词： Moyamoya disease vascular endothelial cells GM-CSF VEGF

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Mitochondrial recruitment in myelin:an anchor for myelin dynamics and plasticity?

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Neural Regeneration Research 2024年第7期19卷 1401-1402页

作者： Jean-David M.Gothié Timothy E.Kennedy Department of neurology and Neurosurgery Montreal Neurological InstituteMcGill UniversityMontrealQCCanada

Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by *** is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered *** is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.

关键词： plasticity insulation dynamics

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Early anticoagulation in patients with stroke and atrial fibrillation is associated with fewer ischaemic lesions at 1 month: the ATTUNE study

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Stroke & vascular neurology 2024年第1期9卷 30-37,I0034页

作者： Angelos Sharobeam Longting Lin Christina Lam Carlos Garcia-Esperon Yash Gawarikar Ronak Patel Matthew Lee-Archer Andrew Wong Michael Roizman Amanda Gilligan Andrew Lee Kee Meng Tan Susan Day Christopher Levi Stephen M Davis Mark Parsons Bernard Yan Melbourne Brain Centre at Royal Melbourne Hospital ParkvilleVictoriaAustralia University of New South Wales South Western Sydney Clinical School LiverpoolNew South WalesAustralia Department of neurology John Hunter HospitalNewcastleNew South WalesAustralia Department of neurology Calvary Public HospitalCanberraAustralian Capital TerritoryAustralia Department of neurology Northern Hospital EppingEppingVictoriaAustralia Department of neurology Royal Brisbane and Women's HospitalHerstonQueenslandAustralia The University of Queensland School of Medicine HerstonQueenslandAustralia Neurosciences Clinical Institute Epworth HealthcareRichmondVirginiaAustralia Department of neurology Austin HealthUniversity of MelbourneHeidelbergVictoriaAustralia Flinders University College of Medicine and Public Health AdelaideSouth AustraliaAustralia Department of neurology Gold Coast University HospitalSouthportQueenslandAustralia The University of Sydney Northern Clinical School St LeonardsNew South WalesAustralia Department of neurology and Neurophysiology Liverpool HospitalLiverpoolNew South WalesAustralia

Background The optimal time to commence anticoagulation in patients with atrial fibrillation(AF)after ischaemic stroke or transient ischaemic attack(TIA)is unclear,with guidelines differing in recommendations.A limitation of previous studies is the focus on clinically overt stroke,rather than radiologically obvious diffusion-weighted imaging ischaemic *** aimed to quantify silent ischaemic lesions and haemorrhages on MRI at 1month in patients commenced on early(5mL,regardless of anticoagulation *** Commencing anticoagulation<4days after stroke or TIA is associated with fewer ischaemic lesions at 1month in AF *** is no increased rate of haemorrhage with early *** results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated w

关键词： patients lesions ischaemic

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Efficacy and safety of Y- 2 sublingual tablet for patients with acute ischaemic stroke: protocol of a phase III randomised double- blind placebo- controlled multicentre trial

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Stroke & vascular neurology 2024年第1期9卷 90-95页

作者： Yu Fu Renhong Tang Rong Chen Anxin Wang Jinsheng Ren Shunwei Zhu Xiaofei Feng Dongsheng Fan Deparment of neurology Peking University Third HospitalBeijingChina State Key Laboratory of neurology and Oncology Drug Development NanjingJiangsuChina Simcere Pharmaceutical Group Limited NanjingJiangsuChina Neurodawn Pharmaceutical Co. LtdNanjingJiangsuChina Department of neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina

Background and purpose Clinical studies have demonstrated that edaravone dexborneol can improve the functional outcomes in patients with acute ischaemic stroke(AIS).The present clinical trial aimed at testing the efficacy and safety of Y-2 sublingual tablet on 90-day functional outcome in patients with *** and design This is a randomised,double-blind,placebo-controlled,multicentre,parallel-group trial of Y-2 sublingual tablet on patients with *** estimated 914 patients at age of 18–80 years with AIS within 48 hours after symptom onset from 40 hospitals will be randomly assigned to receive Y-2 sublingual tablet or placebo for 14 *** are at score 6–20 points on National Institutes of Health Stroke Scale(NIHSS)and had a modified Rankin Scale(mRS)≤1 before this stroke,except mechanical thrombectomy and neuroprotective agents *** outcomes The primary outcome is the proportion of patients with mRS≤1 on day 90 after *** efficacy outcomes include mRS score on day 90,the proportion of patients with mRS≤2 on day 90;the change of NIHSS score from baseline to day 14 and the proportion of patients with NIHSS score≤1 at the days 14,30 and *** This trial will provide valuable evidence for the efficacy and safety of Y-2 sublingual table for improving 90 days the functional outcomes in patients with *** registration number NCT04950920.

关键词： patients protective centre

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Increased retinal venule diameter as a prognostic indicator for recurrent cerebrovascular events:a prospective observational study

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Neural Regeneration Research 2024年第5期19卷 1156-1160页

作者： Ying Zhao Dawei Dong Ding Yan Bing Yang Weirong Gui Man Ke Anding Xu Zefeng Tan Department of neurology and Stroke Center the First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Clinical Neuroscience Institute the First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Department of neurology the First People’s Hospital of FoshanFoshanGuangdong ProvinceChina

Microvasculature of the retina is considered an alternative marker of cerebral vascular risk in healthy ***,the ability of retinal vasculature changes,specifically focusing on retinal vessel diameter,to predict the recurrence of cerebrovascular events in patients with ischemic stroke has not been determined *** previous studies have shown a link between retinal vessel diameter and recurrent cerebrovascular events,they have not incorporated this information into a predictive ***,this study aimed to investigate the relationship between retinal vessel diameter and subsequent cerebrovascular events in patients with acute ischemic ***,we sought to establish a predictive model by combining retinal veessel diameter with traditional risk *** performed a prospective observational study of 141 patients with acute ischemic stroke who were admitted to the First Affiliated Hospital of Jinan *** of these patients underwent digital retinal imaging within 72 hours of admission and were followed up for 3 *** found that,after adjusting for related risk factors,patients with acute ischemic stroke with mean arteriolar diameter within 0.5-1.0 disc diameters of the disc margin(MAD_(0.5-1.0DD))of≥74.14μm and mean venular diameter within 0.5-1.0 disc diameters of the disc margin(MVD_(0.5-1.0DD))of≥83.91μm tended to experience recurrent cerebrovascular *** established three multivariate Cox proportional hazard regression models:model 1 included traditional risk factors,model 2 added MAD_(0.5-1.0DD)to model 1,and model 3 added MVD0.5-1.0DD to model *** 3 had the greatest potential to predict subsequent cerebrovascular events,followed by model 2,and finally model *** findings indicate that combining retinal venular or arteriolar diameter with traditional risk factors could improve the prediction of recurrent cerebrovascular events in patients with acute ischemic stroke,and that retinal imaging c

关键词： acute ischemic stroke arteriolar cerebrovascular events diameter digital retinal imaging microvasculature prediction recurrent retina venular

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In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke

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Neural Regeneration Research 2024年第10期19卷 2240-2248页

作者： Meng Yuan Yao Tang Tianwen Huang Lining Ke En Huang Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Human Anatomy School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Scientific Research Center School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Department of neurology Fujian Medical University Union HospitalFuzhouFujian ProvinceChina Fujian Key Laboratory of vascular Aging Fujian Medical UniversityFuzhouFujian ProvinceChina

In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1(PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.e B-GFAP-sh PTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-sh PTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

关键词： astrocyte in situ direct reprogramming ischemic stroke miR-30 based shRNA neuron polypyrimidine tract-binding protein 1 transdifferentiation

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Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

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Neural Regeneration Research 2024年第7期19卷 1541-1547页

作者： Xingyong Chen Nannan Yao Yanguang Mao Dongyun Xiao Yiyi Huang Xu Zhang Yinzhou Wang Department of neurology Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of neurology Cangzhou Central HospitalCangzhouHebei ProvinceChina Fujian Academy of Medical Science FuzhouFujian ProvinceChina Key Testing Laboratory of Fujian Province FuzhouFujian ProvinceChina

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain ***,the potential links between them following ischemic stroke remain largely *** present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin ***,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia *** r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and *** ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,*** addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/***,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

关键词： blood-brain barrier CYP1B1 oxidative stress oxygen glucose deprivation/reoxygenation tight junction vascular endothelial cells Wnt/β-catenin pathway β-catenin

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Central nervous injury risk factors after endovascular repair of a thoracic aortic aneurysm with type B aortic dissection

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World Journal of Clinical Cases 2024年第22期12卷 4873-4880页

作者： Feng Liang Jie-Qiong Su Department of vascular Surgery Qinghai Province Cardiovascular and Cerebrovascular Disease Specialist HospitalXining 810012Qinghai ProvinceChina Department of neurology Qinghai Province Cardiovascular and Cerebrovascular Disease Specialist HospitalXining 810012Qinghai ProvinceChina

Aortic dissection is the deadliest disease of the cardiovascular *** B aortic dissection accounts for 30%-60%of aortic dissections and is mainly treated by endovascular repair of thoracic endovascular aneurysm repair(TEVAR).However,patients are prone to various complications after surgery,with central nervous system injury being the most common,which seriously affects their prognosis and increases the risk of disability and ***,exploring the risk factors of central nervous system injury after TEVAR can provide a basis for its prevention and *** To investigate the risk factors for central nervous system injury after the repair of a thoracic endovascular aneurysm with type B aortic *** We enrolled 306 patients with type B aortic dissection who underwent TEVAR at our hospital between December 2019 and October *** patients were categorized into injury(n=159)and non-injury(n=147)groups based on central nervous system injury following *** risk factors for central nervous system injury after TEVAR for type B aortic dissection were screened by comparing the two *** logistic regression analysis was *** The Association between age,history of hypertension,blood pH value,surgery,mechanical ventilation,intensive care unit stay,postoperative recovery times on the first day after surgery,and arterial partial pressure of oxygen on the first day after surgery differed substantially(P<0.05).Multivariate logistic regression analysis indicated that age,surgery time,history of hypertension,duration of mechanical ventilation,and intensive care unit stay were independent risk factors for central nervous system injury after TEVAR of type B aortic dissection(P<0.05).CONCLUSION For high-risk patients with central nervous system injury after TEVAR of type B aortic dissection,early intervention measures should be implemented to lower the risk of neurological discomfort following surgery in high-risk patients

关键词： Plateau area Type B aortic dissection Thoracic endovascular aneurysm repair Central nervous system injury Risk factors

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